Achieving Localised Delivery With Magnetic Vectoring - Pharmaceutical Technology

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Achieving Localised Delivery With Magnetic Vectoring
Charles E. Seeney tells us about the possibilities of nanotechnology and magnetism, and how a novel approach could improve localised drug delivery.


Pharmaceutical Technology Europe


Q. How is nanotechnology applied to improve magnetic delivery systems? In which medical applications could it potentially be applied?

Magnetic vectoring can be considered as a two-stage process (at least), in which the MNP-drug construct is first caused to magnetically concentrate at a target site, such as a tumour, using externally shaped magnetic field gradients. Following extravasation where the potential for resistance to drug penetration (tumour interstitial fluid pressure) is overcome, the pro-drug is subsequently cleaved within the tumour microenvironment. Ideally, the MNP-drug construct remains nontoxic until cleaved within the tumour matrix. Additional components, such as affinity-based vectors, can be incorporated onto the construct for improved attachment and uptake (4).

Nanoscale devices and carriers exploit the enhanced permeability and retention effect because they are small enough to traverse pores in the inherently disordered tumour vasculature. In addition, the 'nano' effect of increasing the surface area to volume–mass ratio with decreasing size enables high-drug loading on the particle surface. However, this advantage must be balanced with the retention of adequate magnetic susceptibility to enable magnetic deflection to successfully exit the vasculature.

Current magnetic field technology already allows drugs to be applied to tumours at superficial sites (e.g., close to the skin or gliomas just underneath the skull) (4, 7, 8, 12, 13). We also believe that innovation will enable magnetic field gradients to be constructed with the potential to manipulate MNP-drug constructs at visceral sites, such as the pancreas. It is also envisioned that this platform technology, in addition to localised drug delivery, will be able to open and close sphincters, aid hearing amplification and remediation, and promote controlled muscle movement. Using the biomagnetic switch concept, implanted MNPs can be used to drive tissue movement or vibration in response to an oscillating magnetic field (11). This concept can also be applied, for example, to the treatment of gastrointestinal reflux disorder by magnetically opening and closing the muscle, or in driving middle ear vibrations in response to an auditory input, or perhaps moving impaired muscle such as the blinking of eyelids.

Q. When exploring the possibility of nanotechnology in a medical therapy, what are the potential safety concerns? How are safety issues monitored throughout research?

Safety concerns around nanomedicines have had persistently high visibility in the public domain—much more so than other therapeutics without the "nano" label. Concerns are based on the notion that nanoscale materials may distribute into and persist in anatomical compartments in a way that is not typical for other therapeutic agents. However, research activities, including those based on nanotechnology, are governed and monitored by regulators. At some point in the research process, very early on or after concept validation, the development effort will incorporate studies to address both biodistribution and toxicity effects. This early effort sets the stage for determining the potential viability of the methodology as it progresses through subsequent preclinical studies.

Q. What tools, techniques, equipment and expertise are needed to conduct nano-enabled drug research? Given that nanomedicine is a relatively new field of research, how difficult is to find the right skills, experience and equipment?

Nanotechnology is an enabling technology, in which an ultraminiaturised process, procedure or application has the capacity to run better, faster, more efficiently or more effectively. As a nanotool, this concept can apply to technology development across the spectrum of scientific disciplines; thus, achieving a successful result also requires a merger of scientific skills/disciplines. To address this, both government and academic institutions have established various types of nanotechnology R&D centres/clusters for collaborative efforts, so that the range of required technical skills are seated in a single, discrete location. These clusters also house the expensive basic research and characterization tools, such as atomic force microscopy, electron microscopy, x-ray diffraction, and magnetic instrumentation, which can carry research well through concept validation (14, 15).

Scientists who can understand and merge the concepts and principles of nanotechnology with medicine to develop advanced treatments are definitely in short supply. A successful project in nanomedicine that delivers a new drug targeting technology can incorporate many disciplines including nanophysics, magnetic physics, organic/biochemistry, molecular biology and oncology. Finding a team can require a lot of effort.


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